Francesca E.M. Neuberger North Bristol NHS Trust, Bristol, UK Abnormal liver tests are relatively common, occurring in approximately 3–5% of pregnancies. Due to physiological changes of pregnancy, the reference ranges for liver tests are different in this group. Abnormal liver tests in pregnancy can broadly be divided into three categories; results that can be attributed to pregnancy‐associated disease, and results that are due to non‐pregnancy‐related disease, which may be pre‐existing underlying disease, sometimes unmasked by the pregnancy, or newly acquired. A knowledge of normal pregnancy physiology and pregnancy‐specific conditions enables the clinician to avoid over‐ or under‐investigating pregnant women, so giving the best chance of an optimum pregnancy outcome. Interpretation of liver tests in pregnant women starts with a careful history and examination. Many women will experience some of the symptoms of normal pregnancy, which overlap with those of liver disease (Box 7.1). It is very common to have a degree of lethargy, particularly in the first trimester. It is prudent to exclude anemia as a contributor. The abdominal distension associated with a gravid uterus is usually easily distinguishable from that of ascites or hepatomegaly, but a pregnancy test should be carried out in any women of childbearing age, presenting with this symptom, or any other acute medical presentation. A degree of ankle swelling is also very common, but it needs to be further investigated with a blood pressure check and urine dip to look for the presence of proteinuria, which may indicate pre‐eclampsia, or more rarely an underlying renal disorder (Box 7.2). Pruritus in pregnancy affects approximately one in five women. It warrants further investigation toward the end of pregnancy, with a blood test to measure total bile acids (TBAs), to diagnose/exclude intrahepatic cholestasis of pregnancy (ICP). This condition is most commonly diagnosed in the third trimester, but it can occur as early as eight weeks of gestation. Occasionally, as discussed below, some chronic cholestatic diseases present during pregnancy with pruritus (such as primary sclerosing cholangitis, PSC, and primary biliary cholangitis, PBC). Reference ranges for pregnancy differ from those used for non‐pregnant women. The most common changes in normal pregnancy are an isolated raised alkaline phosphatase (ALP), and a low albumin (Table 7.1). There is a hemodilution effect, resulting in lower normal values for hemoglobin and creatinine. Table 7.2 details suggested initial investigations for pregnant women with unexplained abnormal liver tests. Table 7.1 Reference ranges in pregnancy. Source: Adapted from Nelson‐Piercy [1]. Table 7.2 Investigations in pregnancy. ALP increases over the course of the pregnancy. If it is raised in isolation, a useful test is ALP isoenzymes, which can differentiate placental ALP from other causes of raised ALP (Figure 7.1). Occasionally ALP levels greater than 1000 iu/l are seen in normal pregnancy. If it is not possible to check ALP isoenzymes, it is prudent to perform a basic liver screen (Box 7.3). A normal gamma‐glutamyl transferase would also support an elevated ALP being from a placental source. Albumin drops in normal pregnancy due to hemodilution. If albumin is lower than the reference range, consider proteinuria (which can be excluded with a urine dip), protein losing enteropathy, or liver disease as possible causes. In diagnosing pregnancy‐related liver disease, it is helpful to be mindful of the woman’s gestation, medical history, and obstetric history when considering the differentials. The majority of pregnancy‐related causes of liver disease occur in the third trimester (Table 7.3). It is important to establish the correct diagnosis, not only to guide immediate management, including whether it is prudent to deliver the fetus to aid maternal recovery, but to be able to counsel the woman about potentials risks in future pregnancies. Figure 7.1 Approach to investigating raised alkaline phosphatase (ALP) in pregnancy.
7
Pregnancy
Introduction
Normal Pregnancy
History
Investigations
Non‐pregnant
Pregnant
Trimester
1st
2nd
3rd
Hb (g/l)
120–150
105–140
WBC × 109/l
4–11
6–16
Plts × 109/l
150–400
150–400
MCV (fl)
80–100
80–100
Urea (mmol/l)
2.5–7.5
2.8–4.2
2.5–4.1
2.4–3.8
Creatinine (μmol/l)
65–101
52–76
44–72
55–77
K (mmol/l)
3.5–5
3.3–4.1
Na (mmol/l)
135–145
130–140
Protein creatinine ratio (mg/mmol)
< 30
Bilirubin (μmol/l)
0–17
4–16
3–13
3–14
Total protein (g/l)
64–86
48–64
Albumin (g/l)
35–46
28–37
AST (iu/l)
7–40
10–28
11–29
11–30
ALT (iu/l)
0–40
6–32
GGT (iu/l)
11–50
5–37
5–43
3–41
ALP (iu/l)
30–130
32–100
43–135
133–418
Bile acids (μmol/l)
0–14
0–14
FT4 (pmol/l)
9–26
10–16
9–15.5
8–14.5
FT3 (pmol/l)
2.6–5.7
3–7
3–5.5
2.2–5.5
TSH (mu/l)
0.3–4.2
0–4.5
0.5–3.5
0.5–4
Investigation
Consideration in pregnancy
Liver ultrasound
Safe at any gestation
Chest x‐ray
Safe at any gestation
Liver biopsy
Not contraindicated at any gestation if benefit > risk
Ideally undertaken in second trimester
FibroScan
Not validated in pregnancy
Magnetic resonance imaging
Not contraindicated at any gestation
Computed tomography
Can be performed at any gestation if benefit > risk
The patient must be counseled about radiation exposure to herself and the fetus
Gastroscopy
Safe during pregnancy
Ideally undertaken in second trimester, but can be done at any gestation if indicated
Low‐dose sedation is recommended, and fetal monitoring should be offered pre‐ and post‐procedure
Left lateral position in the second half of pregnancy
Alkaline Phosphatase in Normal Pregnancy
Abnormal Liver Tests Attributable to Pregnancy‐Related Disease
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